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Clinical Manifestations.

Sterre C M de Boer1, Chiara Fenoglio2,3, Andrea Arighi4

  • 1Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, Netherlands.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Females with behavioral variant frontotemporal dementia show higher neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) levels. This suggests females may present with more advanced disease, independent of cognitive reserve.

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Area of Science:

  • Neuroscience
  • Biomarkers
  • Neurodegenerative Diseases

Background:

  • Sex-linked differences in sporadic behavioral variant frontotemporal dementia (s-bvFTD) are increasingly recognized.
  • Females with bvFTD show greater brain atrophy than males, despite similar clinical severity.
  • Brain atrophy correlates with neurodegeneration markers like NfL and GFAP.

Purpose of the Study:

  • To investigate sex differences in serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) levels in s-bvFTD.
  • To determine if these biomarker differences are linked to cognitive reserve.
  • To explore potential implications for disease presentation and progression.

Main Methods:

  • Serum NfL and GFAP levels were measured in 357 participants (275 s-bvFTD, 82 PPD) using Simoa.
  • Biomarker levels were compared between sexes and analyzed using linear regression.
  • Cognitive reserve was assessed in a subset of s-bvFTD participants using a residuals approach.

Main Results:

  • Females with s-bvFTD had significantly higher NfL and GFAP levels than males (p < 0.05).
  • No sex differences in biomarkers were observed in the primary psychiatric disorder (PPD) group.
  • NfL predicted steeper cognitive decline in males compared to females, independent of cognitive reserve.

Conclusions:

  • Females with s-bvFTD exhibit significantly higher NfL and GFAP levels, suggesting potential differences in disease presentation.
  • These sex differences in biomarkers are not explained by variations in cognitive reserve.
  • Findings suggest females with s-bvFTD may present at a more advanced disease stage.